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Linking the FTO obesity rs1421085 variant circuitry to cellular, metabolic and organismal phenotypes in vivo

ABSTRACT: Linking the FTO obesity rs1421085 variant circuitry to cellular, metabolic and organismal phenotypes in vivo

PROVIDER: PRJNA714932 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13979113_1.fastq.gz	Fastqsanger.gz
	SRR13979113_2.fastq.gz	Fastqsanger.gz
	SRR13979114_1.fastq.gz	Fastqsanger.gz
	SRR13979114_2.fastq.gz	Fastqsanger.gz

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Similar Datasets

Linking the FTO obesity rs1421085 variant circuitry to cellular, metabolic, and organismal phenotypes in vivo.

Project description:Variants in FTO have the strongest association with obesity; however, it is still unclear how those noncoding variants mechanistically affect whole-body physiology. We engineered a deletion of the rs1421085 conserved cis-regulatory module (CRM) in mice and confirmed in vivo that the CRM modulates Irx3 and Irx5 gene expression and mitochondrial function in adipocytes. The CRM affects molecular and cellular phenotypes in an adipose depot-dependent manner and affects organismal phenotypes that are relevant for obesity, including decreased high-fat diet-induced weight gain, decreased whole-body fat mass, and decreased skin fat thickness. Last, we connected the CRM to a genetically determined effect on steroid patterns in males that was dependent on nutritional challenge and conserved across mice and humans. Together, our data establish cross-species conservation of the rs1421085 regulatory circuitry at the molecular, cellular, metabolic, and organismal level, revealing previously unknown contextual dependence of the variant's action.

| S-EPMC8294759 | biostudies-literature

Linking the FTO obesity rs1421085 variant circuitry to cellular, metabolic and organismal phenotypes in vivo

Project description:Atac-seq in iWAT pre-adipocytes at day 1 of adipogenic induction

2021-05-01 | GSE169032 | GEO

The Obesity-associated Fto gene regulates activity of the dopaminergic midbrain circuitry [FTO KO]

Project description:Here we use MeRIP-Seq to analyze global adenosine methylation (m6A) in mRNAs in the midbrain and striatum of Fto-deficient mice. We find that Fto deficiency leads to increased methylation within a subset of mRNAs important for neuronal signaling, including many within the dopaminergic signaling pathway. Collectively, our results show that Fto regulates demethylation of specific mRNAs in vivo, and this activity relates to control of dopaminergic transmission. Profiling of m6A in midbrain and striatum from FTO knockout mice

2013-06-15 | E-GEOD-47216 | biostudies-arrayexpress

Obesity-associated variants within FTO form long-range functional connections with IRX3

Project description:Genome-wide association studies in diverse populations have reproducibly associated variants within introns of FTO with increased risk for obesity and type-2 diabetes.While the molecular mechanisms linking these noncoding variants with obesity are not immediately obvious, subsequent studies in mice demonstrated that FTO expression levels influence body mass and composition phenotypes. Yet, no direct connection between the obesity-associated intronic variants and FTO expression or function has been made. We show that the obesity-associated noncoding sequences within FTO are functionally connected, at megabase distances, primarily with the homeobox gene IRX3, rather than with FTO. 4C-seq samples for Fto/fto and Irx3/irx3a genes promoters in different samples: adult mouse brain, E9.5 mouse embryos and 24hpf zebrafish embryos.

2014-02-24 | E-GEOD-52830 | biostudies-arrayexpress

The Obesity-associated Fto gene regulates activity of the dopaminergic midbrain circuitry [WT]

2013-06-15 | E-GEOD-47215 | biostudies-arrayexpress

The Obesity-associated Fto gene regulates activity of the dopaminergic midbrain circuitry [FTO KO]

2013-06-15 | GSE47216 | GEO

The Obesity-associated Fto gene regulates activity of the dopaminergic midbrain circuitry [WT]

2013-06-15 | GSE47215 | GEO

Obesity-associated variants within FTO form long-range functional connections with IRX3

2014-02-24 | GSE52830 | GEO

Next-generation sequencing for the fat mass and obesity-associated protein (FTO) binding mRNA

Project description:Purpose: The goals of this study are to investigate the mRNAs that bind to the FTO protein in the white fat tissue from mice. Methods: 1. White fat from CAG promoter driven transgenic Flag-tagged FTO mice were extracted with RNA protected. 2. Flag-FTO proteins were immunoprecipitated with control IP using IgG. 3. The immunoprecipitated RNAs were deep sequenced and analyzed. Results: We focused on the mRNAs which have functions related to lipid metabolism and homeostasis. Immunoprecipitated RNAs profiles from Flag-FTO IP and IgG IP were generated by deep sequencing.

2016-01-05 | E-GEOD-74255 | biostudies-arrayexpress

Adiponectin-cre FTO flox/flox and FTO flox/flox mouse white fat tissues

Project description:Single nucleotide polymorphisms in intron 1 of the fat mass and obesity-associated (FTO) gene were found to be associated with an increased risk of adult obesity. Enhanced FTO expression in mice leads to hyperphagia, increased fat mass, and higher body weight. Neuronal-specific FTOâ??deleted mice have an identical lean body weight phenotype to global FTO-deleted mice. The physiological role of adipose FTO in the homeostasis of energy regulation remains to be elucidated. We used microarrays to elucidate the metabolic pathways that are regulated by FTO in the white fat. FTO flox/flox and Adiponectin-cre FTO flox/flox (AFO) mice were fed with chow diet. White fat tissues from epididymal adipose pad were harvested under ad lib condition for RNA isolation. Three independent pools of FTO flox/flox and AFO mouse white fat RNA were included in the study.

2016-07-03 | E-GEOD-65098 | biostudies-arrayexpress

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